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Homepage – Forum Forums Research, Clinical Trials, and New Treatments Clinical trial to compare BCG VS GEM/DOC

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  • #45766
    Joe
    Participant

    The new approach, which was developed by Michael O’Donnell, MD, at the University of Iowa over 10 years ago, replaces BCG with a combination of two inexpensive, readily available chemotherapy drugs—gemcitabine and docetaxel (gem/doce). Based on this pioneering research from the UI, other major cancer centers have increasingly adopted this regimen, as well. Most recently, a UI study published in 2022 showed that 82% of patients with high-risk NMIBC who were treated with gem/doce instead of BCG remained cancer-free two years after treatment.  With the very encouraging data, the UI team initiated a large scale randomized clinical trial comparing BCG and gem/doc for newly diagnosed NMIBC (TaHG, T1HG, CIS, TaHG+CIS, or T1HG+CIS) patients.   The project is sponsored by ECOG-ACRIN Cancer Research Group – non profit cancer research organization and collaborator is National Cancer Institute.

    BCG treatment  is comprised of 6 weeks induction treatment +  3 weekly maintenance at months 3, 6, 12, 18, 24, 30, and 36 months

    GEM/DOC treatment is comprised of 6 weeks induction treatment + monthly treatment for 2 years

    Primary Outcome measure is to determine the event free survival (EFS) of BCG naïve high grade NMIBC patients treated with BCG vs GEM/DOC

    Estimated enrollment is 870 participants,   116 study locations across the US but not Canada.

    Actual Study Start Date  :  Feb 7, 2023    Estimated Primary Completion Date : November, 2029

    ClinicalTrial.gov Identifier : NCT055338663  does not say which BCG strain, but I expect it to be MERCK Tice strain BCG (ONCO-TICE) as it is the only BCG approved in the US at this point.  Though Tokyo-172 strain BCG clinical trial has been going on since 2017  as the alternative BCG in the US and may be approved during this BRIDGE trial, I do not think it is included in the trial.

    I was surprised to see this announcement because the clinical trial would consume so much resources as it would take 6 years, 870 patients at 116 study locations.  Those who are involved must have a confidence that GEM/DOC will show similar efficacy but with less side effects compared to BCG, which has been shown by retrospective studies in University of Iowa.

    Incidentally, Vancouver General Hospital started offering GEM/DOC treatment for BCG-unresponsive high risk NMIBC and patients with high risk NMIBC who are intolerant of or ineligible or intravesical BCG.    But, I do not know any hospital than VGH is offering GEM/DOC treatment even though BC Cancer Agency publishes GEM/DOC treatment protocol on their website.   I would love to hear anyone who had received GEM/DOC treatment.  I think  it is because GEM/DOC requires a bit more work by hospital staff.   But,  in the US, GEM/DOC is more established.

    Below describes the GEM/DOC protocol found in BC Cancer Agency’ site.

    Step 1:  Insert urinary catheter and instill gemcitabine (1000mg diluted in saline up to 45ml). Clamp or plug foley (dwell time of 1-2 hours)

    Step 2:  Drain bladder until flow stops  – no nee to irrigate

    Step 3:  Instill docetaxel (35.7mg diluted in saline up to 45 ml).  Clamp or plug foley (dwell time of 1-2 hours)

    Step 4:  Unclamp the catheter and drain urine and drug into the drainage bag, then remove catheter.

    Below describes the cost of Gemcitabine chemotherapy agent and Docetaxel chemotherapy agent. The cost was referenced CADTH.CA.

    Gemcitabine costs $ 0.062 per mg  and docetaxel costs $1.52 per mg.   So, gemcitabine 1000 mg costs  CAD $ 62, and docetaxel 35.7mg costs  CAD$ 57.  The cost of  GEM/DOC per treatment costs  CAD$119, which is actually lower than the cost of BCG per treatment.   In terms of cost, GEM/DOC treatment is economically viable for Canadian Health Care.  The cons of GEM/DOC vs BCG is that it would take 3 hours per treatment and requires a nurse who can handle chemotherapy agents, whereas it takes 30 minutes for BCG treatment.   Nevertheless, Canadian patients those are considered BCG-unresponsive or BCG intolerance deserve GEM/DOC treatment as another option wherever they live in Canada.

    “medicine.uiowa.edu/content/alternative-bladder-cancer-treatment-emerges-amid-worldwide-shortage-standard-care-bcg”

    https://classic.clinicaltrials.gov/ct2/show/NCT05538663”

    #45772
    marysue
    Participant

    Hi Joe:

    The Rockyview Hospital here in Calgary is offering GEM/DOC as an alternative to some patients who have had issues with BCG treatments.  As mentioned earlier in another post, the BCG most offered here is the VERITY brand and many patients including myself experienced horrible bladder inflammation as a side effect.  In my previous rounds of BCG in 2008 and in 2010-12 I was given the TICE brand of BCG.  My side effects from that brand were very tough as well but doable with the help of Tylenol and lots of hot baths and rest.  The side effects were mostly flu like and only a small amount of bladder inflammation and irritation.  I would do those side effects over the bladder inflammation in a heartbeat.

    I had my cysto last Thursday and due to the fact that I still have some potential residual inflammation left over from my VERITY BCG treatments in the spring further bladder instillations are on hold for the next 4 months to give my bladder a chance to finish healing.  My bladder has been cranky on and off all summer.  My uro is fairly convinced that the dark pinkish spot on the front wall of my bladder is inflammation but has told me that he wants to see me in 4 months instead of 6 and if it is still there he will do a biopsy to make sure that it is not cancer.  I believe that it is inflammation because that is where two red spots of inflammation were before I started my first set of maintenance treatments in March. If it is cancer then it will be removed and my follow up will most likely be GEM/DOC.  The nurse told me that they now do get some MERCK BCG in at the clinic but the supply is inconsistent so there would be no guarantee that it would be available instead of the VERITY.  She strongly recommended that I consider giving GEM/DOC a try because patients at the Rockyview clinic seem to have tolerated it better than BCG and have had good results with it.

    I’m nervous to try GEM/DOC simply because of the horrible reaction I had to the Epirubicin post TURBT last year.  My uro reassured me that reaction was due to the fact that my bladder had a raw open wound and if I do GEM/DOC he told me that I would not do treatments until my bladder was completely healed.  I told them I will give it some consideration. I know that I need to find that balance between what I can tolerate and what I can do to prevent further recurrence and risk of progression.  Further decisions will be based on what is seen at my next cysto which I’m expecting to be in January.

    In Calgary, patients stay at the clinic for the GEM/DOC treatments.  It takes about 3 hours -2 for the treatments and an additional hour for prep, consult etc.

    Thanks for the info Joe.  As always, it is very informative.  (((HUGS)))

    #45773
    Joe
    Participant

    Hi Marysue,

    Thanks for sharing your experience and about GEM/DOC in Calgary.  I am glad to know that GEM/DOC is being offered there for BCG intolerance, perhaps also for BCG unresponsive.  Do you know the hospital was motivated to offer GEM/DOC because of increased incidents of more severe side effects by VERITY-BCG?    I think you and a few others are in unique position who were treated with Onco-TICE, then later treated with VERITY-BCG, so can share differences in experience if there are any.  New patients cannot tell.  Hospitals/urologist can tell differences if there are any.  I was concerned, as I had posted, tha a hospital in New Zealand published their clinical experience that higher number of patients who had to terminate BCG treatment by SII Onco-BCG (Russian strain)  which the hospital used when MERCK OncoTICE BCG (TICE stain) became shortage.  As mentioned before, VERITY-BCG is actually SII-Onco-BCG, which VERITY-BCG imports from SII in India.  So, I was concerned that the same thing could happen in Canada.   There is a reason to substantiate the concern.  The concern was difference in the number of bacteria instilled to bladder could be much higher with VERITY-BCG than Onco-TICE.  SII Onco-BCG prescription label says that the number of bacteria contained in a 40mg vial is between 1×10**8 CFU and 19.2×10**8 CFU or in average 9.6×10**8 CFU , whereas MERCK Onco-TICE prescription label says the number of bacteria contained is 50mg vial is between 1×10**8 CFU and 8×10**8 CFU or in average 4×10**8.  The reason why the number of bacteria even among vials of the same manufacturer is because BCG is live bacteria it is very difficult to come up with the same number if bacteria.  So the manufacturer can only guarantee the range in number of bacteria in a given vial.   If we compare a vial of OncoTICE BCG (50mg)  and a vial of VERITY-BCG(40mg), a vial of VERITY- BCG(40mg) contains in average twice more bacteria than a vail of OncoTICE(50mg).   Furthermore, t he full dose recommended for VERITY-BCG is two vials or 80mg.  So, technically, it is possible the full dose of  VERITY-BCG can contain in average 4 times more bacteria than the number of bacteria a full dose of OncoTICE (50mg) contains.  Given everything equal, of course, VERITY-BCG could cause severer side effects if side effects and the number of bacteria instilled to bladder are correlated.  Actually, I had asked Health Canada if they could share the data which they actually tested bacteria counts for Onco-TICE BCG and VERITY-BCG.  I never received the data.     Merck said that their new production facility with 3 times more production capacity will be ready between late 2025 and late 2026.  So, in three years, every Canadian patients should be able to access MERCK Onco-TICE BCG.  Until then, I sincerely hope that CUA comes up the country wide uniform recommendation how patients should be treated with two different BCGs.

     

     

    #45780
    marysue
    Participant

    Hi Joe:

    In answer to your question – yes in Calgary GEM/DOC became the new thing to give bladder cancer patients diagnosed with high grade non-muscle invasive bladder cancer.  First because of the BCG shortage and then secondly due to the large number of patients who like myself could not tolerate the VERITY BCG.  When I was at my cysto check in March, I had a discussion with my uro and nurse back then about the differences in side effects between the two BCGs.  Mind you, I do know of patients that did have massive bladder inflammation with the TICE BCG.  As mentioned for me the TICE brand caused far more flu like side effects.  The one thing that intensified those side effects was that I was in full throttle menopause at the time.

    Back in March I did bring up the issue about the VERITY potentially being much stronger than the TICE and did ask why they wouldn’t consider giving a half dose of VERITY which would have been roughly equivalent to a full dose of TICE but couldn’t get any answers.  I mentioned if they did that maybe fewer patients would have bad side effects.  The main thing I have heard about the VERITY is what I experienced – extreme bladder inflammation and the other thing that goes with that is that the inflammation is very slow to heal.  One lady from the Women’s Only support group is nearly a year out from her last VERITY BCG treatments and is still dealing with severe inflammation.  Her bladder is so badly damaged that it has lost its elasticity and she now has a very overactive bladder and is still bleeding from time to time.  Her uro is recommending an RC to end her misery. When I had some irritation and inflammation from the TICE it healed up within 2-3 weeks.  I’m going on 6 months since my last treatment and still have inflammation in my bladder. I do not want to end up in the situation like the lady in our group.

    I do know that there was a lot of dickering between the clinic nurses and the hospital pharmacy when it came to reducing the dosage of VERITY BCG. My uro gave the go ahead for me to have a reduced dosage of BCG for my maintenance treatments. We agreed on a quarter dose. Apparently it is supposed to be difficult to divide down the dosage due to the way it is packaged or the size of the vials.  I told them that was BS and to just get on with the math.  I told them since a full dose of VERITY was two vials then a quarter dose was simply half a vial.  They couldn’t decide about whether the remaining liquid amount should be saline or just put the quarter dose into my bladder as is.  I told them when I had a dosage reduction of the TICE back in 2011 the nurses made up the difference of the liquid with the saline so maybe it should be the same with the VERITY.  Why they don’t have this figured out is beyond me. At any rate it still didn’t work for me because I had some remaining inflammation in my bladder from the induction set and even the quarter dose made it worse.

    My game plan for the future if all is clear at my next cysto and if my uro agrees, is to leave my bladder alone and just go for checkups every few months.  If I have a recurrence, I will have a TURBT and give GEM/DOC a go if follow up treatments are recommended.

    Despite all the misadventures, I still believe in immunotherapy.  To me it makes far more sense to do something to stimulate one’s immune system to ward off cancer rather than continually having a chemical substance put in your body which may or may not kill off the cancer.

    I truly hope that MERCK will be able to get up and running sooner rather than later so Canadian bladder cancer patients will have a safe and reliable source of BCG.  Right now no one seems to have any concrete answers about the VERITY brand which I strongly believe should be taken off the market.

    It would be nice if the CUA would have some kind of conference and ask patients to attend so they could get our feedback.  I would gladly take part. Anyhow here’s to hoping for some answers like you said. (((HUGS)))

     

    #45788
    Joe
    Participant

    Hi Marysue,

    Thank you always for your prompt answer and other valuable inputs and knowledge.   It sounds like the urology department of your hospital is progressive wiling to adopt newer protocols.    Even a year ago,  Dr. Seth Lerner of Baylor College of Medicine, another known influential urologist was persuading urologists who were attending in conference to use GEM/DOC as it is easy though he understood two drugs and 3 hours are not high throughput procedure.  Kudos to urologists in Rockyview General Hospital.

    I have sensed that dose reduction strategy to cope with BCG side effects is not widely adopted.   BC CANCER AGENCY 1/3-1/2 dose reduction is listed  for induction and maintenance treatment, but I am not sure if every urologist follows the protocol.  Interestingly, BC CANCER AGENCY lists two more different maintenance protocols. i.e. monthly for 6 months, and at 8 weeks and 12 12 weeks, then monthly at 4 – 12 months.  Perhaps, some urologists are still using the protocol they had been using.

    In the US, there is so called Dr. Lamm protocol.  Dr. Lamm said it is also true that maintenance can cause side effects. That is why we always reduce the dose (1/3, 1/10, 1/100th even if needed) or hold treatment if increasing side effects are seen.  As Dr. Morales of Queens University is known to be the father of BCG treatment, Dr. Lamm of Arizona University is know as a Guru of NMBC treatment, especially with BCG.   Incidentally, the Phase 3 clinical trial of PRIME, to see if BCG vaccination before BCG treatment improves outcome and if Tokyo-172 strain BCG performs as good as Onco-TICE was  completed recruitment of about 1000 patients .  I have heard the first report will be out early 2024.    Anyway, Dr. Lerner of Baylor College said not so much for induction treatment, but for maintenance you can get much immune response by reducing dosage.  1. Sometimes less is better  2. An appropriate cytokine response can be achieved with as little as 1/100 of a standard dose. 3. Dose reduce in face of toxicity rather than abandon potentially effective therapy – 1/2, 1/3, 1/10, 1/30, 1/100.

    There is an excellent recent discussion between Dr. Wassin Kassouf, ex chair of BCC medical advisory board & professor at McGill  and Dr. Badrinath R. Konety, professor of Urology at Rush Medical College in Minneapolis.  I would recommend everyone to watch it.    The title of discussion is Optimizing BCG Therapy in Bladder Cancer: Expert Insights on Managing Toxicity and Maximizing Efficacy.    Dr. Konety mentioned that he prescribed Quinolone antibiotics 6 hours after and 12 hours after every BCG treatment. He said it would reduce side effects by 20%.  I have heard the same thing by Dr. Ashish Kamat of MD Andersons.  A brand name of quinolone antibiotics is Ofloxacin.   Ofloxacin was mentioned as a treatment of side effects in Canada, but not as preventive for side effects as mentioned  by Dr. Konety or Dr. Kamat.   Anyway, Ofloxacin is oral pill, so except the cost of medicine, it will should not add burden to healthcare in Canada.

    https://tinyurl.com/4c6jw7ph”

    Lastly, yes, you will be one of best person to represent patients with NMIBC to participate in discussion in regards to treatment.  Another person can be me:)

    #45792
    marysue
    Participant

    Hi Joe:

    Thanks once again for all the information.  It is great.

    There is so much to be studied about bladder cancer and its treatments.  Doctors seem to focus how effective a particular drug is and its side effects and not much else.  While all that is important, I believe that some research needs to be done just for women re age, hormones, any previous surgeries ie. hysterectomy or urological surgeries and how does any of that play into their bladder cancer diagnosis and proposed treatment options. Our genetics and physiology is different from men and I want to know how those differences could affect our ability to tolerate treatments, outcomes etc.

    And as mentioned if we are expected to use more than one type of BCG for the time being, look into the bacteria count of each type of BCG and create a standard dosage between the different types of BCG.

    If doctors can come up with something to take as a preventative or as treatment to protect the bladder from severe inflammation that would be amazing. It would help many more patients complete the treatment protocols.

    I realize that the type of research that I’m suggesting would take a lot of time, money, people and resources that may not be available at the moment,  but I’m hopeful at some point at least a portion of what I’ve mentioned would be considered.  (((HUGS)))

    #45832
    Nightingale
    Keymaster

    Hi Joe & MarySue,

    The update from the head of our Urology in Hamilton is this.  Sequential Gem-Doc combination is currently in front of inpatient pharmacy for approval.  Also, there are other drugs around the corner for this clinical issue including Nadoferagene.

    My best,

    #45838
    Joe
    Participant

    Hi Nightingale,

    Thanks for updating what’s happening in Ottawa.  Its great that GEM-DOC protocol is becoming available for patients in Ottawa too.  I think GEM-DOC will be available eventually to major hospitals in Canada.  The next step is to have GEM-DOC accessable to patients being treated local hospitals.   RIght now in BC, some patients have to travel long distance to go to a major cancer cenre to have GEM-DOC treatment, which I think inefficient.

    #45839
    marysue
    Participant

    Hi Joe:

    I have heard of many patients in several provinces having to travel long distances to receive bladder treatments either BCG, Mitomycin C and probably it would be the same now for GEM/DOC.  The main issue is lack of trained personnel in smaller communities.  Back when I had my in person support group going here in Calgary, I heard of some people that came into Calgary the night before their treatments and would check into a hotel, go for the treatment, do their 2 hour holding the treatment at the hotel, then void out, clean the bathroom, check out and then head home.  Still others would do the holding of the BCG while on the road.

    All of this is not ideal and adds to the out of pocket costs for patients which for some may be prohibitive.  In my mind it is not safe to be on the road with BCG inside you because if you have a car accident and are injured and not able to let the emergency people know they may be exposed to BCG or if the BCG stays inside you and you can’t tell people that the drug is in there then if it is in there too long it could seriously damage your bladder. The only “blessing” with GEM/DOC is that you usually stay at the clinic for the treatments because it involves two drugs.  One is placed in the bladder and then after about an hour drained out and then the other is put in for the next hour.  Still for many, they may not be too comfortable after having had two drugs in their bladder and then have to try to manage a long drive home.

    I know that I’m asking the impossible but in a perfect world, it would be nice if smaller communities had trained staff at their urgent care centers or even at certain doctor’s offices where a patient could go instead of driving long distances.

    A high school friend of mine lives on Vancouver Island just south of Nanaimo.  During the pandemic in 2020, she discovered that she had a recurrence of breast cancer.  For 30 days straight she had to drive to Victoria, catch the ferry to Vancouver and then find a way to the clinic, have her radiation treatment and then make the journey back home again.  How she managed that I have no idea.  I asked her if there was a clinic or hospital where she could stay nearer to where she was having treatments and she told me no.  She could have found a hotel room as a few were still open for things like medical situations but the cost for the hotel was prohibitive so she elected to drive back and for everyday.  This could have been avoided if there was a clinic closer to home.  I shudder when I think of the risk of exposure she faced on top of the arduous journey.

    I would love to live in an smaller community but because of having to deal with bladder cancer I’m staying put in Calgary.

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